Alice T. Shaw, MD, PhD, an attending physician in the Center for Thoracic Cancers at Massachusetts General Hospital, discusses the two most advanced next-generation ALK-inhibitors for the treatment of non-small cell lung cancer (NSCLC): LDK378 and alectinib (AF802). Both agents currently have Breakthrough Therapy designation status.
LDK378 has the most data available and has gone through phase I testing. In a phase I trial, LDK378 demonstrated a response rate of about 60% and median progression-free survival of 8.3 months in ALK-positive patients who had relapsed on crizotinib. This “impressive activity,” Shaw says, has given way to phase II and III trials. LDK378 (ceritinib; Zykadia) was granted an accelerated approval on April 29, 2014 (See more >>>
Alectinib has been studied in a crizotinib-naïve population in Japan. Shaw says a 93% response rate was reported in this population. Alectinib is being analyzed in crizotinib-resistant patients and early data is showing a 50-60% response rate.
Both LDK378 and alectinib have also shown activity in brain metastases and leptomeningeal disease, which are typically difficult to treat.